Macrocyclic lactones, and in particular, the “macrolides” are naturally derived and semi-synthetic compounds that are anti-bacterial, anti-inflammatory and also potentially able to modify ion transport (Saint-Criq et al. 2011 B). These biological activities have resulted in the use of Azithromycin, for a wide range of inflammatory diseases mediated by neutrophil activation. In particular, azithromycin is used to decrease airway inflammation and mucus hyper-secretion in patients with diffuse panbronchiolitis, chronic sinusitis, and chronic bronchitis. These properties have also led to the long-term use of azithromycin in cystic fibrosis (CF) where it is unclear whether its primary effect is on airway secretion properties, or on anti-bacterial effects on opportunistic pathogens such as Psuedomonas aeruginosa. 
Given the observed efficacy of macrolides, notably azithromycin, in various lung diseases, we sought to solve two problems associated with their use. The first is to limit selection for antibiotic resistance associated with long-term use of the material. The second was to identify convenient formulations for inhaled or oral use. In particular, formulations or salts that are particularly soluble in biological solutions.
In a recent disclosure (61/391,679), we described the fact that oxidized descladinosyl macrolides were non-antibacterial in vivo while retaining desirable anti-inflammatory activity especially in lung inflammation. In the process of optimizing the use of macrolides in lung inflammation, we observed that organic salts of macrolides are more soluble in NaCl containing solutions and more suitable for promoting Cl-efflux from cells.
Here we describe novel salts of macrolides with improved solubility, novel pro-drugs of macrolides with improved solubility and associated uses for the treatment of inflammatory diseases of lung, liver, muscle and eye.